A significant part of the H ion produced systemically is excreted by the kidney with NH3 as NH4 ion. In metabolic acidosis or with severe total body K ion depletion, a renal adaptive mechanism is induced, resulting in an enhanced renal synthesis of NH3 from glutamine thus amplifying the kidneys' ability to enhance H ion excretion. This project was designed to elucidate the mechanism(s) and control factor(s) involved in the adaptive effect and to explore the relative significance of the various biochemical steps involved in renal mitochondrial NH3 production. Renal cortical mitochondria isolated from either acidotic or K ion depleted rats have been incubated in vitro in media containing glutamine in various concentrations to reproduce the adaptive effect and to study concentrations on mitochondria and incubation media of various substrates involved in NH3 formation. Mitochondria isolated in tandem from normal rats have been studied in parallel companion incubations where the pH or K ion concentration was varied in an effort to reproduce the cytoplasmic millieu induced by either acidosis or in vivo K ion depletion. BIBLIOGRAPHIC REFERENCE: Tannen, R.L. and Kunin, A.S. Effect of pH on ammonia production by renal mitochondria. Am. J. Physiol. 231:1631, 1976.